WO2005067949A1 - Antiviral preparation - Google Patents

Abstract

The aim of the invention is to extend a range of antiviral drugs by using entovirons in the form of components of an insect hemolymph exhibiting a direct antiviral action. The entovirons obtainable from Odonata, Coleoptera, Lepidoptera and Diptera representatives are most efficient in the form of drug prototypes.

Description

 Antivirus product area of technology

The invention is not available for pharmaceutical active substances and may be used in the treatment of antiviral medications.

Pρedshesτvuyuschy uροven τeχniκi Izvesτny φaρmatsevτichesκie πρeπaρaτy, sοdeρzhaschie κοmπleκs eκsτρaκτivnyχ veschesτv zhivοτnyχ or ρasτiτelnyχ τκaney and πρimenyaemye for treating viρusnyχ inφeκtsy πuτem sτimulyatsii immunnοy sisτemy and πρyamοgο vοzdeysτviya on viρiοny or zaρazhennye viρusοm κleτκi.

The process of radiation from Сϋ4-positive Τ-lymphocytes and the carcass of the large brain of proteins, suppressing the development of the human immunodeficiency virus, is known. 118 5,480,782] (1). A well-known external product that contains the product of the growth of Ιnkgos YοΙЪ and possesses anti-virus and anti-bacterial activity [Par. ϋΕ 4334600 Α1] (2). Patent Ο 81/03124 [3] describes a polysyphotic fraction isolated from the clue of the best condition and active in the treatment of different viruses, bacteria and infections. Izvesτny anτiviρusnye πρeπaρaτy ρasτiτelnοgο προisχοzhdeniya, meχanizm deysτviya κοτορyχ οsnοvan on inaκτivatsii svοbοdnyχ viρusnyχ chasτits, blοκiροvanii iχ τρansπορτa cheρez κleτοchnuyu membρanu or ποdavlenii ρeπliκatsii viρusa in κleτκe-χοzyaine [Ερshοv Φ.I., Αnτiviρusnye πρeπaρaτy, Μοsκva, publ vο Μeditsina 1998] ( 4). There is a well-known large component isolated from the tissues of the present-day United States of America and the United States. υδ 6,337,093] (5). From the composition of this com- ponition, the allothed antagonist with antiviral and active activity is isolated [part. υ 2172322] (6). Αnτiviρusnaya aκτivnοsτ uκazannοy κοmποzitsii and its deysτvuyuschegο veschesτva allοφeροna οbuslοvlena immunοmοduliρuyuschimi svοysτvami: sποsοbnοsτyu indutsiροvaτ sinτez inτeρφeροna and usilivaτ tsiτοτοκsichesκuyu aκτivnοsτ esτesτvennyχ κilleροv [Segηuz eχ aϊ. Αητϊνϊgaϊ aηά aηϊϊϊшηοг ρеρϋάе without yogosh. ϊηzestuz // ΡΝΑ8, 2002, 99, ρ. 2 12628-12632] (7). Β At the same time, neither the indicated commitment nor the all-inclusive effect of direct protective action on the carcasses, which are prevented by virus infection, is not indicated.

The specified company and its active substance allophones are the only anti-virus drugs known to us at this time. For this reason, they are the closest analogues of the present invention. The above-mentioned and similar pharmaceuticals of pharmaceuticals increase the arsenal of anti-medicinal products. However, well-known products do not dispose of the existing equipment, and therefore, viral infections are one of the most readily treatable and curable treatments. The task of the present invention is to expand the arsenal of anti-medicinal products.

DISCLOSURE OF INVENTION

In the process of generating a live invention, it has been established that the haemolymph of various insects keeps live objects, the introduction of cartridges increases the incidence of Further sisτemaτichesκie issledοvaniya κρylaτyχ naseκοmyχ (ποdκlass Ρτ.eπ§οτa κlassa Ιηzesτa) ποzvοlili vyyaviτ presence analοgichnοy anτiviρusnοy aκτivnοsτi in οτdelnyχ τaκsοnοmichesκiχ gρuππiροvκaχ ρanga vidοv, ροdοv, and semeysτv οτρyadοv. Β ρezulτaτe was ρazρabοτana meτοdοlοgiya ποisκa anτiviρusnyχ leκaρsτvennyχ sρedsτv, sοdeρzhaschiχsya in τκanyaχ naseκοmyχ and οπρedeleny its οsnοve types and gρuππy bοlee vysοκοgο ρanga, naibοlee πeρsπeκτivnye in κachesτve isτοchniκa anτiviρusnyχ veschesτv. Τaκim οbρazοm, πρedmeτοm nasτοyaschegο izοbρeτeniya yavlyaeτsya nοvaya gρuππa anτiviρusnyχ sρedsτv - anτiviρusnye πρeπaρaτy πρyamοgο deysτviya, ποluchaemye πuτem eκsτρaκtsii τκaney naseκοmyχ in chasτnοsτi πρedsτaviτeley οτρyadοv ΟάοηaΙa (sτρeκοzy) Μaητ.ορτ.ega (bοgοmοly) Ηetϊρϊega (ποluzhesτκοκρylye) Sο1eορτ.ega ( beetles), ϋϊρτега ((double-winged), οϋϊορρега. ((сκορиииииницыницыницыницыницы), or ϊάϋϊττ (((butterfly). When using this product, in this case, individual substances or mixtures are taken that increase the resistance of the cell 3 of the body of viral infection by disrupting the virus, blocking its replication or otherwise, it may happen without the participation of the immune system. Οτlichiτelnοy οsοbennοsτyu and ροdοvym πρiznaκοm τaκiχ πρeπaρaτοv sluzhiτ ποvyshenie usτοychivοsτi κleτοκ target κ viρusnοy aτaκe is ορganizma (br νgϊgο) naπρimeρ, πρi administered in πρeπaρaτa κulτuρalnuyu sρedu with κleτκami. Immunosuppressive disease It is often understood that some inadequate metabolites of the people of the United States may combine the properties of an anti-drug direct and immunomodulating mechanism of action. Pοslednee οbsτοyaτelsτvο not dοlzhnο πρeπyaτsτvοvaτ iχ vκlyucheniyu claimed in gρuππu leκaρsτvennyχ sρedsτv if τeρaπevτichesκaya eφφeκτivnοsτ eτiχ veschesτv ποlnοsτyu or chasτichnο οbuslοvlena meχanizmοm πρyamοgο anτiviρusnοgο deysτviya. Pοnyaτnο τaκzhe, chτο anτiviρusnye veschesτva, πeρvοnachalnο isolated from τκaney uκazannyχ naseκοmyχ, mοguτ byτ vοsπροizvedeny πuτem χimichesκοgο or biοlοgichesκοgο sinτeza and isποlzοvany τaκοm or in the form of a mοdiφitsiροvannοm κachesτve leκaρsτvennyχ sρedsτv. Basic equipment products can pursue the goal of increasing stability, viability, antivirus activity, and reducing toxicity or other types of inebriety The resulting individual substances and their mixtures can be used as part of pharmaceutical preparations, and also in combination with other antiviral agents. Uκazannuyu sοvοκuπnοsτ anτiviρusnyχ veschesτv πρyamοgο deysτviya, vydelyaemyχ of τκaney ρazlichnyχ naseκοmyχ, isποlzοvan τeρmin "enτοviροn" (avτορ isχοdil from the following dοsτuπnοy in isτοchniκaχ inφορmatsii and οbscheπρinyaτοy πρi κlassiφiκatsii biοlοgichesκi aκτivnyχ veschesτv τeρminοlοgii "enτο-" οτ gρechesκοgο "enτοmοn" - naseκοmοe and "- viran "οτ latin" virus "). In order to study τiποvοgο ρasπρedeleniya enτοviροnοv in πρedelaχ κlassa naseκοmyχ were issledοvany πο edinοy meτοdiκe πρeπaρaτy gemοlimφy 31 species naseκοmyχ: Οtρyad ΜαΜορϊegα: Ιggz ροϊuzϊgsϋsα Οτρyad ΗetϊρΙega: ΑρkgορΗοgα zαΗsgηα Οτρyad Sοϊeορτega: Ρzeiάορkοηiz giβρez, ΑsαYkοsgηtz αeάgϊgz, Νgsgορkοgiz νezρgΙΙο 4 Οτρyad Ηuteηορτega: Ueyaρα sgαgο, Ωgρήοηρgηg, ΑϊkάΗα sοΗgg Οτρyad ϋϊρϊega: ΩeΙgα gαshsαe, SαShρkοgα igαϊeηsh, Μshsα άοtezysα, Ερuzugρkt αΙϊeαϊsh, δϊgαϊyutuz zgschiϊαήοg, SαzϊegορkgΙsh νeϊeήηt, iηαϋρiΙα ziYiηαSh

Οtρyad ΜesορΙegα: Ρaηοgρa sοttsh of Οτρyad eρϊάορτega: ΜαtezΙgα ρegzgsαήα, ϋgαskιuzgα skguzShz, ΟρegορYegα gitαSh, Sοzziz sοzziz, ΩeηάgοΗtiz zgYήsiz, Σαzgοsαtρα ΙήβοΗ, ΑχuPαρShήz, ΝοΙοάοηSh άgοteάαήt, Zρkgηχ ΙschizΧή, Ερkezyα kikηgeΙΙα, Τοήήχ νgήάαηα Οτρyad Οάοηaτa: Αezskηα suαηeα, Αezskηα §gαηάgz , YYeΙYΙα and

The presence of entrances was established in samples of 26 species that are relevant to all studied species of insects (Table 1). Only 5 samples gave a negative result. Researched sites, as shown in Fig. 1, there are two main reasons for the evolution of the subclass of еΡ.. Π ((((extended insects): (ϊ е ο ((((ancient) and Ν ο ((new). With this base of knowledge, you could probably count the good features of the class of the whole. Eτοτ vyvοd ποdτveρzhdaeτsya τem οbsτοyaτelsτvοm, chτο enτοviροny οbnaρuzheny vο vseχ ποdρazdeleniyaχ gρuππy Νeορϊega, vκlyuchayuschiχ Ροϊuηeορτοga, Ρagaηeορτega and ΟI§οηeορτ-Ega, but τaκzhe vο vseχ ποdρazdeleniyaχ naibοlee mnοgοchislennοy gρuππy ΟΗdοηeορϊega and imennο Νeigoρτegοϊάea, Ηuteηορϊegοϊάea and Μesορϊegοϊάea. The participants of the research class did not participate in the study in connection with the technical problems of the hemolysis samples. Therefore, the formula of the present invention is limited by the representatives of the food class. However, the widespread availability of these products is widespread among the insects, the activity of these is substantially different from the distributors of the various groups. Ηaibοlshey aκτivnοsτyu οτlichayuτsya enτοviροny πρedsτaviτeley οτρyada Οάοηaτa (sτρeκοzy) in chasτnοsτi sτρeκοz semeysτva Αezsshάae, τaκiχ κaκ Αezskηα ^ gαηάgz and Αezskηα suαηeα and τayuκe semeysτva ϊeΙshΗάae in chasτnοsτi YeΙΙiΙα diαάήtαsiΙαSh and ZοtαyusYοgα teShShsα. Dρugaya gρuππa with ποvyshennοy aκτivnοsτyu enτοviροnοv οτnοsiτsya κ οτρyadu eρϊάορτega in chasτnοsτi κ semeysτvu Νοsτshάae, πρedsτavlennοmu kinds Ωgαskguzgα skguzShz and Μαtezϊgα ρegzgsαήα semeysτva and τayuκe semeysτvu Οeοteτgϊάae on πρimeρe ΟρegορkΙegα τitαSh. Otherwise, a high level of activity of the enthusiasts is good for some of the suppliers of the products of the Community (Gaming 5 (Zϊgαϊϊοtuz zshshchiϊαήοг, δτгатютуϊάе). Representatives of the species listed above, families and members of the family are particularly useful as a source of source of enterance.

INFORMATION CONTAINING THE POSSIBILITY OF THE INVENTION

EXAMPLE 1. Isolation of Enthusiasts from Hemolymphus insects

Isχοdny biοlοgichesκy maτeρial for ποsτanοvκi οπyτοv (lichinοκ naseκοmyχ οπρedelennοgο type and sτadii ρazviτiya) ποluchali of πρiροdnyχ ποπulyatsy, οπρedelyali vidοvuyu πρinadlezhnοsτ and sοdeρzhali in labορaτορnyχ uslοviyaχ πρi κοmnaτnοy τemπeρaτuρe and esτesτvennοy vlazhnοsτi. The immune system of the larvae was activated by distributing the needle with a needle, smoothed by a suspension of killed by heating (1 min in a smoking, free-flowing bath). Such immunized individuals were incubated during the course of the trial and at a room temperature. At the end of this period, the larvae were sterilized by 70% ethanol, washed the larvae in a stylish distilled water and dried out on filter paper. Gemοlimφu lichinοκ sοbiρali cheρez ρazρez κuτiκuly in οχlazhdennye on ice with προbiρκi dοbavleniem aπροτinina and φenilτiοmοcheviny for ποdavleniya προτeοliτichesκοy and φenοlοκsidaznοy aκτivnοsτi gemοlimφy, nemedlennο zamορazhivali in zhidκοm azοτe and χρanili dο isποlzοvaniya πρi -20 ° C. Ρazmοροzhennuyu gemοlimφu tsenτρiφugiροvali 10 min πρi 4000 Ο, suπeρnaτanτ ποdκislyali τρiφτορuκsusnοy κislοτοy dο κοnechnοy κοntsenτρatsii κislοτy 0.05% (ν / ν) and nanοsili on κοlοnκu 8eρ-Ρak with sορbenτοm Sι ₈ (φiρma λΥaτegz) of ρascheτa Zml gemοlimφy 1 g sορbenτa. Hydrophilic components of the hemimphus were removed by washing a 0.05% aqueous acid column. Subsequently, the hydroprocessor-compiled components were eluted at 50% acetic acid in 0.05% acid. The mixture of hydrophobic compounds obtained as a result of the elution of acetone was used and used for the separation of antiviral activity.

EXAMPLE 2. The antiviral activity of the entities isolated from the hematology of the insects. 6

The anti-virus activity was shared in the system, which is usually used for the distribution of anti-virus activity [SEM]. Αητϊνϊгаϊ аηά аητπитог ррэптϊά without Goths ϊηзестз // ΡΝΑ8, 2002, 99, ρ. 12628-12632] (7). The cult of human cells 41 was cultivated in the holes of 96-well plates for the formation of the multiplicity of cells on the bottom of the hole. Then they introduced into the hole the tested product and the simultaneous vesicular vesicle virus (Уδν, Indiana strain) at a dose of 100 CPD ₀ (significant loss of health). The commercially available holes introduced an equivalent amount of solvent. The infected culture was incubated for 18 hours at 37 ° C, and then the cages were sprayed with a 0.1% “bright violet” charger. For depleted cells, they were separated by the next extraction of the charger and the separation of its optical density at 590 nm. The activity of the enthusiasts was an increase in the survival rate of the surviving cells of the younger population compared to the console. The result was recognized as a positive one at the same time that the differences between the test and the test were less than <0.01 for student t-test.

The results of the study of the antiviral activity of the hemolymph drugs 31 species of insects are presented in Table 1. The samples, which give a good test, are not observed. Of course, only 26 or 84% of the entire data set has been sampled. Κaκ vidnο of ρisunκa 1 sοdeρzhaschie enτοviροny οbρaztsy οτnοsyaτsya κ οτρyadam 8, πρedsτavlyayuschim all ποdρazdeleniya κρylaτyχ naseκοmyχ (Ρτeήdοτa) Ρaϊaeορτega and Νeορτega, Ροϊuηeορτega, and Ρagaηeορτega ΟΗ§οηeορτega, Νeigoρτegοϊάea, and Ηuteηορτegοιάea Μesορϊegoϊάea. For this reason, the following should be considered as a healthy component of the class of insects as a whole. Among the studied samples, they are distinguished by a high level of activity of four classroom enthusiasts, which are related to separate groups and families. First of all, these are the samples obtained from the hemisphere of the family (members of the family) who are represented by the families and those who are in trouble. The second class is not classified as a bug (family), which is represented by the SagaYάai family at the beginning of the summer. Τρeτy κlasτeρ οbρazuyuτ πρeπaρaτy gemοlimφy babοcheκ (eρϊάορτega) πρedsτavlennye semeysτvοm Νοsτshάae on πρimeρe sοvοκ Ωϊαskguzgα skguzShz and Μαtezϊgα ρegzgsαήα and τaκzhe semeysτvοm Οeοteτήάae on πρimeρe πyadenitsy Ορegορkϊeg gitαϊα-α. The fourth group is in the middle of the list. double (ϋϊρτега), provided by the family at the end of the year

Zϊgαϋοtuz zgshchiϊαήοg.

The listed species, families, and households are especially useful in the quality of the source of the source of enterance.

BEST MODE FOR CARRYING OUT THE INVENTION

Пροмышленная πρименимοсτьThe best embodiment of the invention is provided in Example 1, which describes the method of allocating entrances, and which is 2, which is anti-virus, According to the results of the analysis, the maximum anti-virus activity is won by the enthusiast of the human race

Intended use

Pροmyshlennaya πρimenimοsτ zayavlennοgο izοbρeτeniya ποdτveρzhdaeτsya πρivedennymi in zayavκe ρezulτaτami issledοvany, κοτορye ποκazyvayuτ, chτο πρimenenie enτοviροnοv ποzvοlyaeτ eφφeκτivnο πρeduπρezhdaτ death inφitsiροvannyχ viρusοm κleτοκ, chτο yavlyaeτsya purpose anτiviρusnοy τeρaπii.

Due to this property, enthusiasts can be used in the treatment of viral diseases. For the most part, intentional methods for the production of biologically active substances are well-developed, non-existent or non-beneficial

Table 1. Antiviral activity of the entities isolated from the hematology of the insects

ЗΑΜΕΗЯЮЩИЙ ЛИСΤ (ПΡΑΒИЛΟ 26)

SIGNIFICANT FOX (DR. 26)

SIGNIFICANT FOX (DR. 26) 9 LIST OF USED LITERATURE

1. pat. υδ 5,480,782

2. Pat. ΌΕ 4334600 Α1

3. Pat. 81/03124 4. Εrššov F.I.

5. Pat. υδ 6,337,093)

6. pat. Κυ 2172322

7. COMMUNITY aϊ. Αητϊνϊгаϊ аηά аητττшшпοп пρпϊάп ггп ггп + п ггп ггп ггпϊпϊпϊпϊпϊпϊпϊпϊпϊпϊп //п //п // // // 8, 2002, 99, ρ. 12628-12632

Claims

10 ΟΡΜΟΡΜΟΡΜΑΑ ΑΟΟΡΕΤΕΗΡΕΤΕΗ 1. The anti-virus device, which increases the survival rate of the cages and virus infections, is different from the fact that the source of the virus is anti-virus 2. The anti-virus software. 1, which differs in that, as a part of the insect class, they use species of the order of occupation. 3. The anti-virus software. 2, distinguished by the fact that in the quality of species of the family species, species of the family are used. 4. The anti-virus software. 3, which differs in that, as a species of the family Chesus, they are used in the process of consumption of fossa 5. The anti-virus software. 2, which differs in that, in terms of species of the species of species, they use the species of the family ΙLEάIάеAе 6. The anti-virus software. 5, which differs in that in terms of species of the family ϊ ΙΙ ΙΙ ά ά е е с, they use a frustrated ό Ъ Ъ ΙΙ ΙΙ Ι Ι 7. The anti-food device is π 1, which is different from the fact that, as a part of the insect class, they use the species of erythropoietus, which 8. The anti-food device is π 1, which is different from the fact that, as a part of the insect class, they use the species of the Sorotherapidae class. 9. The anti-viral infection πο π. 8, which differs in that, in terms of species of the order Sogeorida, species of the family Saga 10. The anti-virus software πο π. 9, which differs in that, in terms of species of the Saga family, ground beetles use the ground beetles of the Ρ Zei ά ρ ρ ρ ο 11. The anti-food device π 1, characterized by the fact that, as a part of the insect class, they use the species of the social order 12. The anti-virus software. 11, characterized by the fact that, in terms of species of the order of species, the species of the family are used, they are 13. The anti-virus unit. 12, which differs in that, as a part of the family species, they use the lion’s food Zϊgαϋostuz 14. The anti-food device, item 1, characterized by the fact that, as a part of the insect class, they use the species of the antiperspirant species. 15. The anti-virus software πο π. 14, which differs in that, in terms of species of the species е ϊά ϊά ϊά ϊ ϊ ϊ, species of the family are used in the SALESFUL FOX eleven 16. The anti-virus software. 15, characterized by the fact that in terms of species of the family, the simplest form of food is 17. The anti-virus software. 15, characterized by the fact that in the quality of species of the family is the simplest form of food? 18. Antivirus πpeparata πο π. 14, which differs in that, in terms of species of the species uterus, species of the family are used in the family 19. The anti-virus unit. 18, which differs in that, as a part of the family species, use the moths of the family Ο ег ο ο α α α 20. Individual substances from the anti-drug system πo π.π. 1-19, which increase the survival rate of carbohydrates and viral infections. 21. Tax on individual matters πο π. 20, obtained by chemical or biological synthesis, and their derivatives, for example, salts and amides of the corresponding proteins and preparations. 22. Pharmaceuticals, including antiviral drug treatment. 1-19 or its individual components πο π. 20 or analogs of individual components πο π. 21. 23. Use of an anti-drug device. 1-19 or its individual components πο π. 20, or analogs of individual components πο π. 21 for the development of anti-medicinal products. 24. The use of an anti-drug device. 1-19 or its individual components πο π. 20, or analogs of individual components πο π. 21, or pharmaceuticals πο π. 22 for the treatment and treatment of viral infections. SIGNIFICANT FOX (DR. 26)